Modafinil (“MDF”) is currently marketed by Cephalon, Inc. under the trade name PROVIGIL® as a racemic mixture of its R and S enantiomers. PROVIGIL® is used for the treatment of excessive sleepiness associated with narcolepsy, shift work sleep disorder (“SWSD”), and obstructive sleep apnea/hypopnea syndrome (“OSA/HS”).
Studies have shown that while both enantiomers of modafinil are pharmacologically active, the S enantiomer is eliminated from the body three times faster than the R enantiomer. Prisinzano et al., Tetrahedron: Asymmetry, vol. 5 (2004) 1053-1058. It is, therefore, preferable to develop pharmaceutical compositions of the R enantiomer of modafinil, as opposed to its racemic mixture.
The R enantiomer of modafinil is known as armodafinil and has the chemical name (−)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide. The molecular weight of armodafinil is 273.35 and it has the following chemical structure:
Armodafinil is commercially available as NUVIGIL™. Armodafinil is well tolerated and has the safety profile comparable to modafinil.
Armodafinil was first disclosed in the U.S. Pat. No. 4,927,855 (“the '855 patent”) and in EP Publication No. 0233106, both of which are assigned to Lafon Laboratories.
The preparation of armodafinil is also disclosed in the '855 patent and it is summarized in the following scheme:
See '855 patent, col. 2, 11. 16-53.
The process disclosed in the '855 patent uses (−)α-methylbenzylamine in the resolution step. Furthermore, two additional crystallization steps are performed in order to increase the enantiomeric purity of the modafinic acid. As a consequence, the overall yield of 32% reported in the '855 patent is rather unsatisfactory for large scale commercial use.
During the preparation of armodafinil, an impurity, bis(diphenylmethyl)disulfide (“R-MDF-DS”) may be formed. R-MDF-DS has the following structure:

PCT Publication No. WO 2007/103221 describes a process for the preparation of bis(diphenylmethyl)disulfide (“R-MDF-DS”) and a process for reducing the amount of R-MDF-DS in armodafinil comprising suspending armodafinil in C5 to Cl2 hydrocarbon. PCT Publication No. WO2007/103221 relates, among other aspects, to armodafinil containing less than about 0.2% area by HPLC of bis(diphenylmethyl) disulfide.
Oae, S., “The Organic Chemistry of Sulfur”, Plenum Press, N.Y., 1977, describes the following mechanism for obtaining bis(diphenylmethyl)disulfide, wherein RSH in this case is unstable leading to the disulfide, RSSR, wherein R is alkyl or aryl.

Given the low yields and disulfide impurities present in the processes of the prior art, there is a need in the art for improved processes for obtaining optically and chemically pure armodafinil substantially free of disulfide impurities that will be suitable for industrial scale synthesis.